Lycopene Prevents DEHP-Induced Leydig Cell Damage with the Nrf2 Antioxidant Signaling Pathway in Mice

As a plasticizer, di­(2-ethylhexyl) phthalate (DEHP) is the most usually used phthalate. Leydig cell is a male-specific cell, which plays a principal role in spermatogenesis and masculinization by the androgens of synthesis and secretion. Numerous researchers have indicated that DEHP can result in testicular toxicity by inducing oxidative stress. Lycopene (LYC) is a possible treatment option for male infertility due to its natural antioxidant properties. Our study was aimed to investigate whether LYC could rescue DEHP-induced Leydig cell damage. The mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) and/or LYC (5 mg/kg BW/day) for 28 days. We found that LYC attenuated DEHP-induced Leydig cell damage. Moreover, the protective role of LYC was verified by the histopathological and ultrastructural analysis of the Leydig cell. LYC suppressed oxidative stress that was induced by DEHP. In the Leydig cell, the expressions of the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes were improved through LYC-mediated protection in DEHP-induced Leydig cell damage. Our findings indicated that LYC could increase the antioxidant capacity via mediating Nrf2 signaling pathway, thereby attenuating DEHP-induced Leydig cell damage.